scholarly journals Elevated serum uric acid is a facilitating mechanism for insulin resistance mediated accumulation of visceral adipose tissue

2020 ◽  
Author(s):  
Luisa Fernández-Chirino ◽  
Neftali Eduardo Antonio-Villa ◽  
Arsenio Vargas-Vázquez ◽  
Paloma Almeda-Valdés ◽  
Donají Gómez-Velasco ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Visceral Adipose Tissue ◽  
Visceral Obesity ◽  
Causal Mechanism ◽  
Mediation Analyses ◽  
Bidirectional Relationship ◽  
Visceral Adipose

BACKGROUND: Serum uric acid (SUA) has a relationship with cardiometabolic conditions such as insulin resistance (IR) and visceral adipose tissue (VAT) accumulation. Here, we aimed to clarify the nature of this relationship and the underlying causality mechanism. METHODS: We conducted a population-based cross-sectional study comprising 8,504 subjects joining both NHANES 2003-2004 and 2011-2012 cycles and ENSANUT Medio Camino 2016. We performed mixed effects linear regression models using HOMA2-IR, adipoIR, and METS-VF as indicators of IR and VAT accumulation. Furthermore, we performed mediation analyses to assess a potential causal mechanism and ROC curves to establish cut-off points for identification of IR and visceral obesity using SUA. Finally, with an additional dataset comprised of 226 subjects with both euglycemic hyperinsulinemic clamp (EHC) and dual X-ray absorptiometry (DXA) measurements for IR and VAT accumulation, we performed a network of confirmatory mediation analyses. RESULTS:We found that SUA has a mediating role inside the bidirectional relationship between IR and visceral obesity, and it is part of an underlying causality mechanism which includes adiponectin. The proportion of the mechanism mediated by SUA is greater when stated that IR (in either peripheral or adipose tissue) leads to VAT accumulation (14.90%[13.20%-17.00%] and 15.54%[13.61% - 18.00%] to 4.88%[3.06%-7.00%] and 8.13%[5.91% - 10.00%]) instead of the opposite direction. This result was confirmed by mediation analyses using gold-standard measurements. CONCLUSIONS:Elevated SUA acts as mediator inside the bidirectional relationship between IR andVAT accumulation. Its role appears to be larger when considering adipose tissue IR as the promoter for VAT accumulation.

scholarly journals Elevated Serum Uric Acid Is a Facilitating Mechanism for Insulin Resistance Mediated Accumulation of Visceral Adipose Tissue

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A44-A45
Author(s):  
Luisa Fernandez-Chirino ◽  
Neftali Eduardo Antonio-Villa ◽  
Omar Yaxmehen Bello-Chavolla ◽  
Paloma Almeda-Valdes
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Visceral Adipose Tissue ◽  
Visceral Obesity ◽  
Mediation Analyses ◽  
Bidirectional Relationship ◽  
Males And Females ◽  
Visceral Adipose

Abstract Background: Serum uric acid (SUA) is related to cardiometabolic conditions such as insulin resistance (IR) and visceral adipose tissue (VAT) accumulation, which have a thoroughly explored bidirectional relationship. Here, we aimed to clarify the nature of the role uric acid plays inside this relationship, alongside the underlying causality mechanism. Methods: We conducted a population-based cross-sectional study comprising 8,504 subjects from a joint cohort composed from both NHANES 2003–2004 and 2011–2012 cycles and ENSANUT Medio Camino 2016. We performed mixed effects linear regression models using HOMA2-IR, adipoIR, and METS-VF as indicators of both peripheral and adipose tissue IR and VAT accumulation, indicating the subject’s cohort of origin as a random effect. Furthermore, we performed multiple mediation analyses to assess a potential causal mechanism and ROC curves to establish cut-off points for identification of IR and visceral obesity using SUA. Finally, with an additional dataset comprised of 226 subjects with both euglycemic hyperinsulinemic clamp (EHC) and dual X-ray absorptiometry (DXA) measurements for IR and VAT accumulation, we performed a network of confirmatory mediation analyses including adiponectin measurements. Results: We found that SUA has a mediating role inside the bidirectional relationship between IR and visceral obesity, and it is part of an underlying causality mechanism which includes adiponectin. The proportion of the mechanism mediated by SUA is greater when stated that IR (in either peripheral or adipose tissue) leads to VAT accumulation (14.90%[13.20%-17.00%] and 15.54%[13.61%-18.00%]) instead of the opposite direction (4.88%[3.06%-7.00%] and 8.13%[5.91%-10.00%]). This result was strengthened by a mediation analysis network using the gold-standard measurements where we observed that the joint effect of SUA and adiponectin mediated 16.32% [8.84%-26.00%] for the effect of IR and VAT accumulation and 12.52% [3.23%-23.00%] in the opposite direction. Cut-off points for SUA to predict peripheral IR were 6.1 mg/dL and 4.8 mg/dL, for males and females respectively. For visceral obesity, cut-offs were 6.4 mg/dL and 4.8 mg/dL for males and females. SUA had a high negative predictive value for all assessments. Conclusions: Elevated SUA acts as mediator inside the bidirectional relationship between IR and VAT accumulation. Its role appears to be larger when considering adipose tissue IR as the promoter for VAT accumulation.

scholarly journals Elevated serum uric acid is a facilitating mechanism for insulin resistance mediated accumulation of visceral adipose tissue

2022 ◽  
Author(s):  
Luisa Fernández‐Chirino ◽  
Neftali Eduardo Antonio‐Villa ◽  
Carlos A. Fermín‐Martínez ◽  
Alejandro Márquez‐Salinas ◽  
Enrique C. Guerra ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Visceral Adipose Tissue ◽  
Elevated Serum ◽  
Visceral Adipose

scholarly journals Abdominal adipocyte populations in women with visceral obesity

2016 ◽  
Vol 174 (2) ◽  
pp. 227-239 ◽  
Author(s):  
Andréanne Michaud ◽  
Sofia Laforest ◽  
Mélissa Pelletier ◽  
Mélanie Nadeau ◽  
Serge Simard ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Visceral Obesity ◽  
Resistance Index ◽  
Small Cells ◽  
Central Feature ◽  
Model Assessment ◽  
Insulin Resistance Index ◽  
Visceral Adipose

BackgroundVisceral obesity is independently related to numerous cardiometabolic alterations, with adipose tissue dysfunction as a central feature.ObjectiveTo examine whether omental (OM) and subcutaneous (SC) adipocyte size populations in women relate to visceral obesity, cardiometabolic risk factors and adipocyte lipolysis independent of total adiposity.Design and methodsOM and SC fat samples were obtained during gynecological surgery in 60 women (mean age, 46.1±5.9 years; mean BMI, 27.1±4.5 kg/m2(range, 20.3–41.1 kg/m2)). Fresh samples were treated with osmium tetroxide and were analyzed with a Multisizer Coulter. Cell size distributions were computed for each sample with exponential and Gaussian function fits.ResultsComputed tomography-measured visceral fat accumulation was the best predictor of larger cell populations as well as the percentage of small cells in both OM and SC fat (P<0.0001 for all). Accordingly, women with visceral obesity had larger cells in the main population and higher proportion of small adipocytes independent of total adiposity (P≤0.05). Using linear regression analysis, we found that women characterized by larger-than-predicted adipocytes in either OM or SC adipose tissue presented higher visceral adipose tissue area, increased percentage of small cells and homeostasis model assessment insulin resistance index as well as higher OM adipocyte isoproterenol-, forskolin- and dbcAMP-stimulated lipolysis compared to women with smaller-than-predicted adipocytes, independent of total adiposity (P≤0.05).ConclusionExcess visceral adipose tissue accumulation is a strong marker of both adipocyte hypertrophy and increased number of small cells in either fat compartment, which relates to higher insulin resistance index and lipolytic response, independent of total adiposity.

Contribution of Visceral Obesity to the Insulin Resistance Syndrome

2001 ◽  
Vol 26 (3) ◽  
pp. 273-290 ◽  
Author(s):  
Simone Lemieux
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Significant Proportion ◽  
Visceral Obesity ◽  
Insulin Resistance Syndrome ◽  
Tissue Accumulation ◽  
Age Related ◽  
Insulin Homeostasis ◽  
Visceral Adipose

A high visceral adipose tissue accumulation has been associated with many metabolic perturbations typical of the insulin resistance syndrome, such as dyslipidemia, impaired glucose-insulin homeostasis, hypertension, and impaired fibrinolysis. It has been documented that male gender, aging, and a hyperglycemic state are conditions that increase the likelihood of displaying features of the insulin resistance syndrome. Accordingly, studies have demonstrated that the variation in visceral adipose tissue accumulation explains a significant proportion of the gender differences in the metabolic risk profile. Age-related differences in metabolic components of the insulin resistance syndrome have also been shown to be partly explained by the concomitant increase in visceral adipose tissue accumulation found with age. Studies have suggested that a high visceral adipose tissue accumulation contributes significantly to the deterioration in the plasma lipid-lipoprotein profile found in hyperglycemic subjects. Finally, it appears that the clustering of metabolic alterations of the insulin resistance syndrome is more pronounced in obese subjects with high levels of visceral fat than in those with a lower visceral adipose tissue accumulation. Key Words: abdominal fat, dyslipidemia, glucose-insulin homeostasis, type 2 diabetes, cardiovascular disease

scholarly journals Fructose Induces Visceral Adipose Tissue Inflammation and Insulin Resistance Even Without Development of Obesity in Adult Female but Not in Male Rats

2021 ◽  
Vol 8 ◽  
Author(s):  
Sanja Kovačević ◽  
Jelena Brkljačić ◽  
Danijela Vojnović Milutinović ◽  
Ljupka Gligorovska ◽  
Biljana Bursać ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Uric Acid ◽  
Energy Intake ◽  
Visceral Adipose Tissue ◽  
Insulin Signaling ◽  
Metabolic Disorders ◽  
Male Rats ◽  
Plasma Uric Acid ◽  
Visceral Adipose

Introduction: Obesity and related metabolic disturbances are frequently related to modern lifestyle and are characterized by excessive fructose intake. Visceral adipose tissue (VAT) inflammation has a central role in the development of insulin resistance, type 2 diabetes (T2D), and metabolic syndrome. Since sex-related differences in susceptibility and progression of metabolic disorders are not yet fully understood, our aim was to examine inflammation and insulin signaling in VAT of fructose-fed female and male adult rats.Methods: We analyzed effects of 9-week 10% fructose-enriched diet on energy intake, VAT mass and histology, and systemic insulin sensitivity. VAT insulin signaling and markers of VAT inflammation, and antioxidative defense status were also evaluated.Results: The fructose diet had no effect on VAT mass and systemic insulin signaling in the female and male rats, while it raised plasma uric acid, increased PPARγ level in the VAT, and initiated the development of a distinctive population of small adipocytes in the females. Also, adipose tissue insulin resistance, evidenced by increased PTP1B and insulin receptor substrate 1 (IRS1) inhibitory phosphorylation and decreased Akt activity, was detected. In addition, fructose stimulated the nuclear accumulation of NFκB, increased expression of proinflammatory cytokines (IL-1β, IL-6, and TNFα), and protein level of macrophage marker F4/80, superoxide dismutase 1, and glutathione reductase. In contrast to the females, the fructose diet had no effect on plasma uric acid and VAT inflammation in the male rats, but less prominent alterations in VAT insulin signaling were observed.Conclusion: Even though dietary fructose did not elicit changes in energy intake and led to obesity in the females, it initiated the proliferation of small-sized adipocytes capable of storing fats further. In contrast to the males, this state of VAT was accompanied with enhanced inflammation, which most likely contributed to the development of insulin resistance. The observed distinction could possibly originate from sex-related differences in uric acid metabolism. Our results suggest that VAT inflammation could precede obesity and start even before the measurable increase in VAT mass, making it a silent risk factor for the development of T2D. Our results emphasize that adipose tissue dysfunction, rather than its simple enlargement, could significantly contribute to the onset and development of obesity and related metabolic disorders.

scholarly journals Protocatechuic acids protects against high glucose- induced insulin resistance in human visceral adipose tissue

2016 ◽  
Vol 62 (5) ◽  
pp. 45-46
Author(s):  
Paulina Ormazabal ◽  
Beatrice Scazzocchio ◽  
Rosaria Varì ◽  
Annunziata Iacovelli ◽  
Roberta Masella
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
High Glucose ◽  
Protective Role ◽  
Insulin Sensitizer ◽  
20 Nm ◽  
Visceral Adipose

Adipocytes exposed to high glucose concentrations exhibit impaired insulin signaling. Binding of insulin to its membrane receptor activates insulin metabolic pathway leading to IRS-1 and AKT phosphorylations. The accumulation of visceral adipose tissue (VAT) correlates with insulin resistance and metabolic syndrome. Anthocyanins (ACN) are bioactive food compounds of great nutritional interest. We have shown that protocatechuic acid (PCA), a major metabolite of ACN, might exert insulin-sensitizer activities in human visceral adipose tissue. The aim of this work was to define the protective role of PCA against insulin-resistance induced by high glucose in VAT.Methodology: VAT obtained from control subject (BMI≤25) were separated in four experimental groups: i) PCA: samples treated for 24 h with 100 μM PCA, ii) GLU: VAT treated with 30 mM glucose for 24 h, iii) PCA+GLU: 1 hour incubation with 100 μM PCA before adding glucose (30 mM, 24 h), iv) CTR: vehicle. After treatment, VAT groups were (or not) acutely stimulated with insulin (20 nM, 20 min). Tyr-IRS-1 and Ser-Akt phosphorylations were assessed by Western blotting (WB) in basal or insulin stimulated tissues in all experimental groups. Samples were assessed for IRS-1, IR, Akt and GLUT4 protein content by WB. Results: No differences in protein contents between experimental groups were found. GLU tissues showed a lower increment in insulin-stimulated phosphorylation of IRS-1 and Akt compared to CTR and PCA samples. This impaired activation was completely reversed by the pretreatment with PCA.Conclusion: An in-vitro insulin-resistance condition induced by high glucose was established in biopsies of VAT. PCA restores the ability of GLU-tissues to fully respond to insulin by increasing IRS-1 and Akt phosphorylations. These results confirm the insulin-sensitizer effect of PCA on VAT previously reported by our group. An anthocyanin rich diet might help to protect against insulin-resistance in VAT.

scholarly journals Abdominal Subcutaneous and Visceral Adipose Tissue and Insulin Resistance in the Framingham Heart Study

Obesity ◽  
2010 ◽  
Vol 18 (11) ◽  
pp. 2191-2198 ◽  
Author(s):  
Sarah R. Preis ◽  
Joseph M. Massaro ◽  
Sander J. Robins ◽  
Udo Hoffmann ◽  
Ramachandran S. Vasan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Framingham Heart Study ◽  
Heart Study ◽  
Visceral Adipose

Abstract P232: Worse Cardiometabolic Health in African Immigrants than African-Americans: Reconsideration of the Healthy Immigrant Effect

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Anne E Sumner ◽  
Michelle Y O'Connor ◽  
Caroline K Thoreson ◽  
Madia Ricks ◽  
Amber B Courville ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
African Americans ◽  
Visceral Adipose Tissue ◽  
African Immigrants ◽  
Cardiometabolic Health ◽  
Sensitivity Index ◽  
Healthy Immigrant Effect ◽  
Immigrant Effect ◽  
Visceral Adipose

In decades past, African immigrants were considered to have better cardiometabolic health than African Americans. Whether this health advantage continues to exist in the 21st century is unknown. To explore differences in markers of cardiometabolic health, oral glucose tolerance tests, blood pressure (BP), visceral adipose tissue (VAT) volume and the waist circumference (WC) which predicts insulin resistance were compared in 210 men (134 African immigrants, 76 African Americans, mean age 36±9y (mean±SD), range 20-64y) who self-identified as healthy. Insulin resistance was defined by the lowest quartile of the insulin sensitivity index (SI≤2•28mU/L-1.min-1). Receiver operating characteristic curves and the Youden Index were used to identify the WC which optimally predicts insulin resistance. BMI was lower in African immigrants than African Americans (27.4±3.9 vs. 29.3±5.5kg/m2, P<0.01). Adjusting for BMI, WC did not differ between groups (93±5 vs. 94±5cm, P=0.55); but African immigrants had more visceral adipose tissue (VAT) (P<0.001) higher BP (P≤0.01), higher fasting glucose (P≤0.001) and 2h glucose (P<0.001) as well as a higher prevalence of previously undiagnosed diabetes (7% (9 of 134) vs. 0% (0 of 76), P<0.01) and pre-diabetes (35% (47 of 134) vs. 22% (17 of 76), P<0.01). Degree of insulin resistance did not differ in African immigrants and African Americans (4.17±2.88 vs. 4.24±2.61 (mU/L)-1 .min-1, P=0.88). Yet, the WC which optimally predicted insulin resistance was lower in African immigrants than African Americans, specifically 92 cm and 102 cm, respectively. As African immigrants had higher VAT, BP and glucose levels than African Americans, the healthy immigrant effect may no longer be a valid concept. As insulin resistance occurred at a lower WC in African immigrants than African Americans, lower BMI in African immigrants does not appear to provide protection from cardiometabolic risk.

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